A Monotherapy Study to Evaluate the Efficacy and Safety of 2 Dose Levels of Albiglutide in Japanese Subjects With Type 2 Diabetes Mellitus (T2DM)

Phase 3

Completed

Conditions: Diabetes Mellitus, Type 2

Interventions: Drug: Albiglutide 30 mg weekly
Drug: Albiglutide 50 mg weekly
Drug: Liraglutide 0.9 mg daily
Drug: Placebo

Registration Number: NCT01733758

Lead Sponsor: GlaxoSmithKline

Brief Summary: This study is designed to examine the efficacy and safety of 2 dose levels of weekly subcutaneously injected albiglutide compared with placebo and an open label reference arm of daily subcutaneous injections of liraglutide, in Japanese subjects with Type 2 diabetes mellitus.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 494

Inclusion Criteria

Subjects with diagnosis of Type 2 Diabetes Mellitus, treated with diet and exercise or a stable dose of 1 OAD at screening
Body mass index (BMI) 17 to 40 kg/ m^2 inclusive
Subjects who are OAD naïve, HbA1c between 7.0% and 10.0% at Screening and at Visit 2; for subjects who enter the study with 1 OAD, HbA1c between 6.5% and 9.5% at Screening and HbA1c between 7.0% and 10.0% at Visit 2
Creatinine clearance >30 mL/min (calculated using the Cockcroft-Gault formula)

Exclusion Criteria

History of type 1 diabetes mellitus •Female subject is pregnant, lactating, or <6 weeks postpartum•
Clinically significant cardiovascular and/or cerebrovascular disease
Current ongoing symptomatic biliary disease, clinical signs or symptoms of pancreatitis, or a history of chronic or acute pancreatitis, as determined by the investigator
Serum amylase >=3 ×ULN and/or serum lipase >=2 × ULN and/or subject is experiencing any symptoms possibly related to pancreatitis
Prior use of a TZD or GLP-1R agonist within 4 months before Screening

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Albiglutide 30 mg weekly	Albiglutide 30 mg weekly	Subjects will be randomly assigned to double blind albiglutide 30 mg weekly treatment for 52 weeks
Albiglutide 30 mg weekly	Placebo	Subjects will be randomly assigned to double blind albiglutide 30 mg weekly treatment for 52 weeks
Placebo	Placebo	Subjects will be randomly assigned to double blind matching albiglutide placebo administered weekly. Subjects will then cross-over to double-blind treatment with albiglutide 30 mg weekly at Week 24 until Week 52
Albiglutide 50 mg weekly	Albiglutide 50 mg weekly	Subjects will be randomly assigned to double blind albiglutide 50 mg weekly until Week 52
Liraglutide 0.9 mg daily	Liraglutide 0.9 mg daily	Subjects will be randomly assigned to open-label liraglutide for 52 weeks

Primary Outcome Measures

Name	Time	Method
Model-adjusted Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24	Baseline and Week 24	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3 month period. The Baseline HbA1c value is defined as the last nonmissing value before the start of treatment. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. Based on analysis of covariance (ANCOVA): Change at Week 24 = treatment (placebo, albiglutide 30 mg, albiglutide 50 mg) + Baseline HbA1c + prior diabetes therapy + age category (\<65 years versus ≥65 years). Participants who discontinued from study treatment before Week 24 had their last post-Baseline HbA1c carried forward for the analysis unless the value is past 14 days after the last dose of study drug. The open-label liraglutide group was a reference group and not included in the primary endpoint analysis model. Descriptive summary statistics are provided as a separate outcome measure.
Mean HbA1c at Baseline, Week 24, and Change From Baseline at Week 24	Baseline and Week 24	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3 month period. The Baseline HbA1c value is defined as the last nonmissing value before the start of treatment. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. Participants who discontinued from study treatment before Week 24 had their last post-Baseline HbA1c value carried forward for the summary, unless the value was past 14 days after the last dose of study drug. The open-label liraglutide group was a reference group; descriptive statistics comparing albiglutide and liraglutide were exploratory endpoints.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	Baseline and Week 24	FPG is an indicator of efficacy. The Baseline FPG value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the FPG value at Week 24 minus the FPG value at Baseline. Participants who discontinued from study treatment before Week 24 had their last post-Baseline FPG observation carried forward for the summary unless the value was 14 days past the last dose of study drug.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52	Baseline and Week 52	FPG is an indicator of efficacy. The Baseline FPG value is defined as the last non-missing value on or before the start of treatment. Change from Baseline was calculated as the FPG value at Week 52 minus the FPG value at Baseline.
Change From Baseline in Body Weight at Week 24	Baseline and Week 24	The Baseline body weight value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the body weight value at Week 24 minus the value at Baseline. Participants who discontinued from the study treatment before Week 24 had their last non-missing weight carried forward for the summary, unless the value is past 14 days after the last dose of study drug.
Change From Baseline in Body Weight at Week 52	Baseline and Week 52	The Baseline body weight value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the body weight value at Week 52 minus the value at Baseline.
Time to Study Withdrawal Due to Hyperglycemia	Baseline through Week 52	Participants who experienced persistent hyperglycemia after uptitration were to be withdrawn from the study. Hyperglycemia is defined as a fasting plasma glucose (FPG) ≥280 mg/dL (≥15.5 mmol/L) from ≥Week 2 to \<Week 4, ≥250 mg/dL (≥13.9 mmol/L) from ≥Week 4 to \<Week 12, or ≥230 mg/dL (≥12.8 mmol/L) from ≥Week 12 to \<Week 52, confirmed a second evaluation within 7 days.
Time to Study Withdrawal for Any Reason	Baseline through Week 52	Time to withdrawal was calculated as the number of days between the date of first dose and the date of withdrawal plus 1. Time to withdrawal was summarized by visit.
Change From Baseline in HbA1c at Week 52	Baseline and Week 52	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3- month period. The Baseline HbA1c value is defined as the last non-missing value on or before the start of treatment. Change from Baseline was calculated as the value at Week 52 minus the value at Baseline.
Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 24	Week 24	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3 month period. Clinically meaningful levels of response in HbA1c are defined as \<6.5% and \<7.0%. Participants who discontinued the study before Week 24 had their last post-Baseline HbA1c value carried forwrad for the summary unless the value was past 14 days after the last dose of study drug.
Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0%) at Week 52	Week 52	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3 month period. Clinically meaningful levels of response in HbA1c are defined as \<6.5% and \<7.0%.